Spring 2021 Seminar Series: Jeff Klauda
University of Maryland
Host: Kalina Hristova
The interaction profile within and between molecules determines the physical properties observed in experimental bulk measurements. The interaction surface leading to attraction and repulsion forces is the cause for instantaneous motion of molecules. One focus of research in my lab is improving and parameterizing the mathematical description of molecular interaction, known as the force field (FF). I will present our work in improving the lipid FF and new algorithms to systematically develop accurate parameters. Accurate lipid FFs allow for accurate modeling of cellular membranes. This talk will give an example of applying simulations to probe the complex structure and dynamics of the outer layer of the skin (stratum corneum). Although lipids in a lipid bilayer serve as a barrier for cells and their organelles, proteins that reside in the membrane are key to various diseases and virial infection. For the last year, my lab has been involved in studies of SARS-CoV-2 and its spike protein and two accessory proteins (ORF7a and ORF7b). I will briefly discuss our work on the spike protein and its ability to evade antibodies but focus on ORF7a and ORF7b. Prior studies have demonstrated that these proteins localize to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). Furthermore, expression of both proteins is correlated with virulence in vivo; for ORF7a, a direct association with host bone marrow stromal antigen 2 (BST-2) suppresses its anti-viral activity, whereas for ORF7b, the ability to form homooligomers is suggested to be a key mechanism by which it can remain ERGIC associated. However, specific, structural models of these homo- and heterooligomeric interfaces are not known, nor are the key protein-protein interfaces for each. We are using multi-scale modeling and collaborating with Dr. Bryan Berger’s lab at the University of Virginia to probe ORF7a/BST-2 dimeriztaion and the ORF7b homodimerization. Our goal is to better understand the dimerization of these proteins and their function, but ultimately develop a SARS-CoV-2 therapeutic that inhibits protein dimerization and function.
Zoom Seminar Info:
Meeting ID: 982 0915 3548